Diphenols protection

After 7 days, the acute inflammatory response at the implantation site was evaluated. Bisphenol A resulted in a moderate level of irritation at the implantation site and was clearly the least biocompatible test substance. Tyrosine derivatives containing the benzyloxycar-bonyl group caused a slight inflammatory response, while all other tyrosine derivatives produced no abnormal tissue response at all. These observations indicate that tyrosine dipeptide derivatives, even if fully protected, are more biocompatible than BPA, a synthetic diphenol. ... 

In an attempt to identify more biocompatible diphenols for the design of degradable biomaterials, we studied derivatives of tyrosine dipeptide as potential monomers. After protection of the amino terminus and the carboxylic acid terminus, the reactivity of tyrosine dipeptide (Figure 1) could be expected to be similar to the reactivity of industrial diphenols. Thus, derivatives of tyrosine dipeptide could be suitable replacements for BPA in the synthesis of a variety of new polymers that had heretofore not been accessible as biomaterials due to the lack of diphenolic monomers with good biocompatibility. 

In an attempt to identify new, biocompatible diphenols for the synthesis of polyiminocarbonates and polycarbonates, we considered derivatives of tyrosine dipeptide as potential monomers. Our experimental rationale was based on the assumption that a diphenol derived from natural amino acids may be less toxic than many of the industrial diphenols. After protection of the amino and carboxylic acid groups, we expected the dipeptide to be chemically equivalent to conventional diphenols. In preliminary studies (14) this hypothesis was confirmed by the successful preparation of poly(Z-Tyr-Tyr-Et iminocarbonate) from the protected tyrosine dipeptide Z-Tyr-Tyr-Et (Figure 3). Unfortunately, poly (Z-Tyr-Tyr-Et iminocarbonate) was an insoluble, nonprocessible material for which no practical applications could be identified. This result illustrated the difficulty of balancing the requirement for biocompatibility with the need to obtain a material with suitable "engineering" properties. 

Hexestrol Hexestrol, 4,4 -(l,2-diethylethylene)diphenol (28.1.29), is a derivative of a,j3-diphenylethane, and it is a synthetic estrogen. Hexestrol is made in a Wurtz dimerization reaction of l-bromo-l-(4-methoxyphenyl)propane (28.1.27) in the presence of sodium, magnesium, aluminum, or iron. The initial l-bromo-l-(4-methoxyphenyl)propane (28.1.27) is made in turn by addition reaction of hydrogen bromide to 4-methoxy-l-propenylbenzene. Subsequent removal of the methoxy protective groups from the resulting dimerization product (28.1.28) using hydroiodic acid gives hexestrol (28.1.29) [37-43]. 

On the other hand, reductive cleavage of the dienone lactam 91 with chromium(II) chloride gave the dibenz[with lithium aluminum hydride. Deprotection of 76biosynthetic precursor of the Schelhammera alkaloids. Oxidation of the diphenol 76a by potassium ferricyanide in the two-phase system gave the expected 5,7-fused dienone 77 in 61% yield (50). 

Work on improving the thermal resistance and particularly the resistance to carbonization (short circuiting of layers of enameled wires under the influence of temperature) via special glycols led to diphenols [29,30]. Diphenols are not reactive under the conditions of a normal poly(ester-imide) synthesis. In synthesis the lower aliphatic diesters of diphenols were used [29-32]. The use of acid chlorides in the polyester reaction with aromatic OH-groups was also protected by patents [33-35] but it seems unlikely that this reaction was performed on the production scale. 

Industrially, diphenols such as bisphenol A are frequently used in order to increase the stiffness of polymers thanks to their aromatic backbone (Fig. 1.20). However, for biomedical applications diphenols cannot be used as monomers because they are cytotoxic. Tyrosine (2-amino-3-(4-hydroxyphenyl) propanoic acid) is the only major natural nutrient containing an aromatic hydroxyl group. Thus, tyrosine dipeptide (where the terminal amino group and terminal carboxylic group are protected) can be seen as replacing diphenols for biomedical devices. 

In a different approach, photolysis of the brominated diphenolic tetra-hydrobenzylisoquinoline 4, in which the nitrogen function is protected as a urethan, produced the neoproaporphine (or proerythrinadienone) 5 in 347 yield, together with //-ethoxycarbonylnorboldine (6) in 5% yield. Further photolysis of 5 in ethanol containing sodium acetate gave a 447, yield of the aporphine 6. This material could be easily reduced with lithium aluminum hydride to boldine (7), thus providing the first total synthesis of this alkaloid. 

Figure 1 Structures of (A) Bisphenol A, a widely used diphenol in the manufacture of commercial polycarbonate resins (B) tyrosine dipeptide with specific chemical protecting groups Xj and alkyl substituents X9 attached to the N and C termini, respectively.

Phenolic compounds are substrates for polyphenol oxidases. These enzymes hydroxylate monophenols to o-diphenols and also oxidize o-diphenols to o-quinones (cf. 2.3.3.2). o-Quinones can enter into a number of other reactions, thus giving the undesired brown discoloration of fruits and fruit products. Protective measures against discoloration include inactivation of enzymes by heat treatment, use of reductive agents such as SO2 or ascorbic acid, or removal of available oxygen. 

The partially-purified extract oxidised a range of phenolic substrates, and also contained proteinases and amino acid decarboxylases. Preincubation of a toluene-treated soil enzyme preparation for 12h at 37°C did not affect diphenol oxidase activities, ie. the oxidases appeared to be resistant to attack by the coextracted soil proteinases. Addition of hyaluronidase before preincubation also was without effect. Preincubation with the microbial proteinase, Pronase for I8h at 37°C decreased diphenol oxidase activities by 307o, and by 100% when both Pronase and hyaluronidase were added. The results suggested that the polysaccharides associated with the extracted soil oxidases protected the enzymes from proteolysis and may play a role in stabilizing exocellular enzymes in soils. 

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